title: Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells.
abstract: The transcription factors EBF1 and Pax5 have been linked to activation of the B cell lineage program and irreversible loss of alternative lineage potential (commitment), respectively. Here we conditionally deleted Ebf1 in committed pro-B cells after transfer into alymphoid mice. We found that those cells converted into innate lymphoid cells (ILCs) and T cells with variable-diversity-joining (VDJ) rearrangements of loci encoding both B cell and T cell antigen receptors. As intermediates in lineage conversion, Ebf1-deficient CD19(+) cells expressing Pax5 and transcriptional regulators of the ILC and T cell fates were detectable. In particular, genes encoding the transcription factors Id2 and TCF-1 were bound and repressed by EBF1. Thus, both EBF1 and Pax5 are required for B lineage commitment by repressing distinct and common determinants of alternative cell fates.
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Nechanitzky
authors.forename: Duygu
authors.initials: D
authors.lastname: Akbas
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scherer
authors.forename: Ildiko
authors.initials: I
authors.lastname: Györy
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoyler
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Ramamoorthy
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D038041:Lymphopoiesis / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D060152:V(D)J Recombination / Q000235:genetics / Q000276:immunology
chemical_list: C489921:Ebf1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D015534:Trans-Activators; D004247:DNA